The long term goal of this laboratory is to understand function of somatotrophs and the molecular mechanisms involved in the regulation of their gene expression. To accomplish these objectives, a pituitary cell line (rPCO) was established from normal adult rat. The rPCO line exhibits characteristics of somatomammotrophs secret GH and PRL, and in addition it secretes large quantities of other unidentified proteins. In the course of characterizing these proteins, a protein factor(s), distinct from GH and PRL has been detected which promotes long-term growth of mammary epithelial cells. It is proposed that this factor(s) represent a novel pituitary hormone with a growth-promoting effect on the mammary gland. The existence of a pituitary mitogen, distinct from GH and PRL, that controls growth to the mammary gland had been previously postulated on the basis of the in vivo studies using rats and monkeys. This suggests that the factor secreted by rPCO cells represents a physiologically relevant growth- promoting hormone. The major goals of the proposed studies will be to identify this factor(s), call here pituitary mitogenic factor (PMF), and to characterize the regulation of its gene expression and its role as a growth promoter of the mammary epithelium. The following specific aims will be pursued to achieve these goals. 1. Characterization of PMF(s). 2. Molecular cloning of PMF. 3. Characterization of biological role of PMF. and 4. Investigation of hormonal regulation of PMF gene expression. Identification of a novel growth-promoting factor secreted by somatomammotrophs and characterization of its biological functions will contribute to understanding the role of the pituitary in the regulation of growth and development of the mammary gland, and potentially the mechanism of growth induction during neoplastic transformation of mammary epithelial cells.